Immunotherapy

Question 1

2 immune checkpoints

Answer 1

CTLA4 to compete w CD28 for B7
- costimulation

PD1 receptors to bind PDL1 ligand
- for apoptosis;

note Tregs having TGF beta secretion and CTLA4

Question 2

What is our body’s defense against cancer cells

How does cancer evade this [5]

Answer 2

CD8 against cancer antigens

Tumor escapes

• decreases MHC
• increase PDL1, (against PD1 on t cells!)
• increases CTLA4 (compete w CD28 on T cells!)
• increases TGF beta - increase T reg and M2 which is inhibitory
• • hence TGF beta is an inhibitory cytokine
• increases T reg

Question 3

Name some adoptive therapies [4]

Answer 3

Tumor-infiltrating lymphocytes
Dendritic cell vaccines
- Tumor antigen-specific T-cells are activated by dendritic cells, which are ex vivo loaded with tumor antigen(s)
TCR Therapy (engineered T Cells)
Chimeric Antigen Receptors CAR T Cells
- extracellular antigen binding TCR
- intracellular activating function - hence no need MHC

• gen 2 and 3 w co-stimulatory intracellular domains

Question 4

How long does baby myasthenia gravis last?

Answer 4

IgG from mother 3-4 months

after this period Primary Immunodeficiencies can manifest

• SCID, Myasthenia Gravis

Question 5

Type 1 Hypersensitivity pathophysiology

How does Type 1 hypersensitivity presents as

Answer 5

Sensitization

• antigen first trigger Th2 differentiation
• • IL4 then Th2 then IL4, 13 for B cell switching for IgE
• • IL5 for eosinophils // RECALL EOSINOPHILIA

IgE binds to Fc epsilon RI on Mast Cells

2nd encounter

• antigen cross-links bound IgE on Mast Cell
• Mast Cell degranulation
• • histamine
• — Bronchoconstriction, permeability, vasodilation; GI contraction
• • protease
• • lipid mediators
• • cytokines

Asthma
GI tract
- inflammation, blood vessel

• Late phase w cytokines recruiting WBC

Question 6

What Lab tests for Type I HS

Answer 6

Serum IgE

Typtase

Question 7

Type II HS

- example

Answer 7

Hemolytic disease of the newborn

• mother negative, baby positive, father positive
• antiRh enters baby

Question 8

Type III HS

• pathophysiology
• examples

Answer 8

Antigen-Antibody complex, Vasculitis
- frustrated phagocytosis, releases ROS, lysosomal enzymes;

• Arthus Reaction
• Lupus, SLE

Question 9

Type IV HS

- pathophysiology

Answer 9

T cell trigger inflammation by cytokines
CD8 direct host cell killing

Eg
- TST for TB
- Contact dermatitis w Haptens
- late stage for Asthma can involve T cells too
Transplant rejection!

Question 10

Gimme the presentations of inflammation and the biochemistry behind them

Answer 10

Red, Warm, - vasodilation - histamine
Swelling - edema, exudate, increase cellularity, WBC - histamine Leukotriene, Complement
Pain - bradykinin, PG
Loss of function

Fever - IL1, TNF alpha, PG

Question 11

Gimme all necrosis

Answer 11

Coagulative - ischemia, w ghost outlines + loss of nuclei, architecture maintained;; gangrenous necrosis too

Liquefactive - pus; brain infraction // Suppurative
Hemorrhagic Necrosis for LIVER/LUNG

Fat necrosis
Fibrinoid necrosis

TB Caseous necrosis
gummatous necrosis

Question 12

Name causes of Granulomas

Answer 12

TB
Syphilis
Cat-scratch
Sarcoidosis (granulomata in lung)
Foreign body - silica
CROHN DISEASE
- fungi

Question 13

healing physiology?

- whats granulation tissue

Answer 13

Macrophages

• to clear cell debris
• releases cytokines to make ECM
• • ECM w collage, H, acid, proteoglycan
• releases Growth Factor for
• • fibroblasts, myofibroblasts - wound contraction
• • angiogenesis

Granulation tissue
- angiogenesis
- fibroblast and inflammatory cells
ECM collagen